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GI‐safe NSAIDs and the suppression of colon cancer (840.5)
Author(s) -
Lichtenberger Lenard,
Waters David,
Phan Tri,
Dial Elizabeth
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.840.5
Subject(s) - azoxymethane , aspirin , colorectal cancer , medicine , toxicity , ibuprofen , carcinogen , pharmacology , aberrant crypt foci , cancer , in vivo , gastroenterology , chemistry , biology , biochemistry , colonic disease , microbiology and biotechnology
The consumption of NSAIDs is linked with a reduction in cancer incidence, metastasis, and mortality. Our lab has developed a family of phosphatidylcholine (PC)‐associated NSAIDs which have reduced GI toxicity both in animals and humans, while possessing full COX‐inhibitory activity. This study was designed to test whether PC‐NSAIDs may also possess significant chemopreventive action. Methods: 1) MC‐26 colon cancer cells were incubated for 24 hours with (0.1‐2mM) of: Aspirin‐PC, or Ibuprofen‐PC; and 2) Sprague‐Dawley rats were inoculated with the carcinogen, azoxymethane (AOM), followed by daily oral NSAID dosing (20 mg NSAID/kg) and after 4 weeks the animals were evaluated for GI toxicity and colonic aberrant crypt formation (ACF). Results: Each of the PC‐NSAIDs showed direct inhibitory effects on growth of MC‐26 cells at 0.5‐1 mM. In vivo , both Aspirin‐PC and Ibuprofen‐PC significantly reduced colonic ACF in rats pre‐treated with AOM without evidence of GI toxicity. Conclusion: Both Aspirin‐PC and Ibuprofen‐PC demonstrated a direct inhibitory effect on the growth of colon cancer cells in vitro and in carcinogen/AOM‐treated rats, significantly reduced the development of colonic ACF, which is a precursor of colonic dysplasia and cancer, suggesting the potential utility of PC‐NSAIDs in patients at risk for colon cancer/recurrence. Supported by R03 CA 171613 and R41 CA171408. Grant Funding Source : NIH R03CA171613; R41 CA171408